3-carboxy-4-hydroxy-diphenyl and salts thereof



PatentedDec. 26,1933

3-CARBOXY-4-HYDR0XY-DIPHENYL ANDsAL'rs THEREOF Adelbert W. Harvey,Bittsburgh, Pa., assignor to E. R. Squibb & Sons, Brooklyn, N. Y., acorporation of New York No Drawing. Application June 4, 1932.

7 Serial No. 615,473

11 Claims.

This invention relates to 3-carboxy-4-hydroxydiphenyl and salts thereof.It includes the new compounds and a method of preparing them.

3-carboxy1-4-hydroxy-diphenyl hasbeen found valuable as an intermediatein the preparation of various organic compounds and particularlypharmaceuticals.

f It may be made by converting 4-hydroxy-diphenyl into an alkali metalphenolate and then forming the carboxy derivative by treatment withcarbon dioxide under pressure at an elevated temperature. withsubsequentacidification. It is important in thisreaction that thephenolate be extremely dry. Although any of the alkali metal phenolatesmay be formed in carrying out this reaction, the sodium phenolate ispreferred because it is cheaper at the present market prices, and withsodium a high yield oi the 3-carboxyl-hydroxy-diphenyl is obtained.Details ofthe,

preferred method of preparation follow:

1'70 grams of l-hydroxy-diphenyl is converted into the sodium phenolateby heating to boiling with grams of sodium hydroxide in 100-600, cc. ofsolution. The sodium phenolate may be recovered by directevaporationover a free flame or by any other'suitable method of evaporation. Careshould be taken to prevent the solution or the incompletely driedmixture from absorbing any considerable quantity of carbon dioxide.Acidification with carbon dioxide breaksthe phenolate down intosodiumcarbonateand 4-hy-.

droxy-diphenyl. Final drying of the phenolate is carried out in vacuo,about 10 mm, at 180 C.

for some time, usually 5 hours, after no more water is collected in anice trap.

The dry pulverized phenolate is treated with carbon dioxide in anautoclave at approximately pounds per square inch to form the sodiumsalt of 3-carboxy-4-hydroxy-diphenyl. The temperature is held at 110-120C., for one hour, increased to ISO-170 .C., and held at the lattertemperature for 3-4 hours. The reaction product, is placed in 3000-4000cc. of water, heated to boiling, and treatedwithcarbon dioxide until nomore 4-hydroxy-diphenyl is precipitated. It is advantageous to filterthe boiled solution before treating with carbon dioxide to remove anytarry material'present in the product removed from the autoclave. Thesuspension obtained by acidification with carbon dioxide is filtered tovremove the unconverted 4-hydroxy-diphenyl and the S-carboxy-4-hydroxy-diphenyl is then precipitated by acidifying thefiltrate with mineral acid. The product is then filtered oil, washedwith water and dried.

The compound when purified by crystallization from alcohol occurs asfinewhite needles with a melting point of 212.5 to 213.5" C.(corrected). This compound is soluble in alcohol, ether, benzene,chloroform and other organic solvents.

I claim: v

1. Compounds having the general formula 3-COOX 4-hydroxy diphenylwherein X represents hydrogen or an alkali metal.

2. 3-carboxy-4-hydroxy-diphenyl.

3. The mono-sodium salt of B-carboxy--hydroxy-diphenyl.

4. In the manufacture of 3-carboxy-4-hydroxy-diphenyl, the steps whichcomprise converting an alkali metal phenolate from 4-hydroxy-diphenylinto the alkali metal salt of 3- carboxy-4-hydroxy-diphenyl by treatingthe phenolate in an extremely dry condition with carbon dioxide undersup eratmospheric pressure and at reaction temperature.

5. In the manufacture of 3-carboxy-4-hydroxy-diphenyl, the steps whichcomprise converting'the sodium phenolate from -hydroxydiphenyl into thesodium salt of 3-carboxy-4- hydroxy-diphenyl by treating thephenolate inan extremely dry condition with carbon dioxide at a pressure ofapproximately one hundred pounds per square inch at a temperature in theneighborhood of C. and then at a temperature in the neighborhood of 150C.

6. In the manufacture of 3-carboxy-4-hydroxy-diphenyl, the steps whichcomprise converting the sodium phenolate from 4-hydr0xydiphenyl into thesodium salt of 3-carboxy-4- its hydroxy-diphenyl'by treating thephenolate in an extremely dry condition with carbon dioxide ata pressureof about ninety pounds per square inch, first at a temperature of aboutto about C. and then at a temperature of about to about C. r

'7. In the manufacture of B-carboxy-d-hydroxydiphenyl, the steps whichcomprise converting the sodium phenolate from 4-hydroxydiphenyl into thesodium salt of 3-carboxy-4- hydroxy-diphenyl by treating the phenolatein an extremely dry condition with carbon dioxide under a pressure ofabout one hundred pounds per square inch atreaction temperature.

8. The method of preparing 3-carboxy-4-hy- 'ioo droxy-diphenyl whichcomprisesconverting 4-1:

hydroxy-diphenyl into the sodium phenolate, drying the sodium phenolate,converting it to the sodium carboxy-derivative of -hydroxydiphenyl bytreatment with carbon dioxide and then acidifying the product.

9. The method of preparing 3-carboxy-4-hydroxy-diphenyl which comprisesconverting 4- ing with carbon dioxide, and then precipitating the3-carboxy-l-hydroxy-diphenyl by acidification with a mineral acid.

10. The method of separating 4-hydroXy-diphenyl from 3 carboxy 4 hydroxydiphenyl which comprises acidifying an aqueous solution of thealkali-metal phenolate of the former and the alkali-metal salt of thelatter with carbon dioxide so as to precipitate the l-hydroxy-diphenyl.

11. As a new compound, a 5-pheny1sa1icy1ic compound having the generalformula,

OOOX

wherein X represents hydrogen or a metal radical.

ADELBERT W. HARVEY.

